Tunable Photocatalytic Selectivity by Altering the Active Center Microenvironment of an Organic Polymer Photocatalyst

The favored production of one product over another is a major challenge in synthetic chemistry, reducing the formation of byproducts and enhancing atom efficacy. The formation of catalytic species that have differing reactivities based on the substrate being converted, has been targeted to selectively control reactions. Here, we report the production of photocatalytic self-assembled amphiphilic polymers, with either hydrophilic or hydrophobic microenvironments at the reactive center. Benzothiadiazole-based photocatalysts were polymerized into either the hydrophilic or the hydrophobic compartment of a diblock copolymer by RAFT polymerization. The difference in the reactivity of each microenvironment was dictated by the physical properties of the substrate. Stark differences in reactivity were observed for polar substrates, where a hydrophilic microenvironment was favored. Conversely, both microenvironments performed similarly for very hydrophobic substrates, showing that reagent partitioning is not the only factor that drives photocatalytic conversion. Furthermore, the use of secondary swelling solvents allowed an additional reagent exchange between the continuous phase and the heterogeneous photocatalyst, resulting in a significant 5-fold increase in conversion for a radical carbon–carbon coupling.


General Experimental Information
All organic synthesis for the photocatalysts were performed in oven-dried glassware under argon, unless otherwise stated. Polymerization reactions were conducted in 20 mL screw-top vials with a PTFE-membrane cap. Reactions investigating the catalytic activity of the substrates were performed in 4 mL screw-top vials. Reaction temperatures are referred to the ones of the heating/cooling media (aluminium heating block, water cooling), unless otherwise stated. Reagents were purchased from Sigma-Aldrich, Merck, ACROS Organics, Alfa Aesar, TCI and used without further purification. Reactions were conducted, using a PTFE-coated, egg-shaped stir bar at around 1900 rpm. Solvents were removed by rotary evaporation under reduced pressure, heating the solution with a water bath at 40-60 °C. Residual high boiling solvents were removed in vacuo (<1 mbar) at room temperature. Formed compounds were characterized by 1 H-NMR, 13 C-NMR, APCI-MS and GC-MS. Throughout all experiments Millipore quality water (Milli-Q-Synthesis 230 V/50 Hz, Milli-Q Q-Gard®2, 18.2 MΩ cm) was used, unless stated otherwise.

General Analytical Techniques
1 H-and 13 C-NMR spectra were recorded at room temperature on a Bruker AVIII 300 spectrometer ( 1 H: 400.13 MHz; 13 C: S 4 100.62 MHz), in deuterated solvents (> 99.5 Deuteration) purchased from Sigma-Aldrich, stored at 4 °C (CDCl3, CD2Cl2, DMSO-d6, D2O). Chemical shifts (δ) for 1 H and 13 C NMR spectra were referenced against TMS (tetramethylsilane) and are given in parts per million (ppm). First order multiplicities in 1 H NMR signals were reported using the following abbreviations: s = singlet, d = doublet, t = triplet, q = quartet, p = quintet, h =sextet; m = multiplet, br = broad signal. Data processing of NMR spectra was done with MestReNova 14.2.3. APCI-MS were recorded on an Advion ASAP (Advion Inc., Ithaca) with DART injection. Fourier-transform infrared spectroscopy measurements were conducted using a Bruker Vertex 70 (Bruker Inc. , Billerica), using a well dispersed, homogenous mixture of 2 mg sample together with 200 mg of KBr (dried and spectroscopic grade) to from stable KBr discs with a Perkin Elmer hydraulic press (15 tons pressure, 4 min), aided by a high vacuum pump. Data processing of obtained FTIR spectra was done with Bruker OPUS 7.8 software.

Photophysical Analytical Techniques
Absorption spectra were recorded with an Agilent Cary 60 UV/Vis spectrometer with xenon light source, using response time 0.04 s, 1.5 nm spectral bandwidth in 0.5 nm intervals and baseline correction. All measurements were conducted in 10x10 mm VWR ES-quartz cuvettes (dimensions: 12.5×12.5×45 mm) fitted with PTFE caps. Emission spectra were recorded with on a J&M Tidas FL3005SL fluorescence spectrometer with a Perkin Elmer diode array (300-1100 nm). Data analysis was conducted by fitting with a Gaussian function and normalization using Origin 2019b (V. 9.65). EPR (Electron Paramagnetic Resonance) was measured on a Magnettech Miniscope MS200 spectrometer at room temperature, microwave frequency: 9.391 GHz, microwave power: 10 mW, modulation amplitude: 9.8 G, field modulation: 0.2 mT at 100 kHz, scan time: 60 s.

Macromolecular Analytical Techniques
GPC experiments were performed using an PSS SECcurity 2 instrument consisting of a pump, auto sampler and column oven .A column set consisting of 3 columns: GRAM 1000 Å , GRAM 1000Å and GRAM 100Å (PSS Standards Service GmbH, Mainz, Germany), all of 300 x 8 mm and 10 µm average particle size were used at a flow rate of 1.0 mL/min and a column temperature of 60 °C. As eluent DMF with 1 g/L LiBr was used. The samples having 1 mg/ml concentration were filtered prior to measurement through 0.45 µm PTFE filter. The injection volume was 100 μL. Detection was accomplished with a RI detector and UV detector at 270 nm wavelength.
Data acquisition and evaluation was performed using PSS WINGPC UniChrom (PSS Polymer Standards Service GmbH, Mainz, Germany). Calibration was carried out by using poly(methyl methacrylate) provided by PSS Polymer Standards Service GmbH (Mainz, Germany).

Solvents
Dry solvents DMSO, DMF and toluene were bought from ACROS Organics, containing H2O <50 ppm, stored under activated molecular sieves of 3 Å pore diameter and transferred within an argon counter stream. P.a. grade triethylamine was purchased from Sigma-Aldrich, with a purity of ≥99.5%, stored under identical conditions to dry solvents. Solvents for flash column chromatography (EtOAc, Chloroform, n-Hexane, CH2Cl2 and MeOH) were purchased in technical grade and used without further purification.

Photoreactor Setup
All photochemical reactions were performed within the customized photoreactor depicted in Figure

General Synthetic Procedures
Photocatalytic polymer stock solution was prepared freshly before every reaction. Therefore, the polymer was dissolved in Milli-Q water (10 mg polymer/300 µL water, 75.3 µg photocatalyst) and sonicated for 20 min. After cooling down, the solution was used straight away.

Photocatalytic Sulfide Oxidation
For each reaction, polymer stock solution (300 µL, 10 mg polymer, 75.3 µg photocatalyst) was given into a 4 mL screw-cap vial, equipped with a stir bar. Followed by addition of water (Milli-Q, 1.7 mL) and the sulfide substrate to give a 10 mM solution (0.3 mol% photocatalyst). Under constant stirring at 450 rpm, and cooling to 15 °C, the vials were placed into a photoreactor slot and irradiated with blue light for 24 h. Afterwards, each sample was analysed according to the GC/MS procedure.

Photocatalytic Imine Formation
For each reaction, polymer stock solution (300 µL, 10 mg polymer, 75.3 µg photocatalyst) was given into a 4 mL screw-cap vial, equipped with a stir bar. Followed by addition of water (Milli-Q, 1.7 mL) and the amine substrate to give a 5 mM solution(0.6 mol% photocatalyst). Under constant stirring at 450 rpm, and cooling to 15 °C, the vials were placed into a photoreactor slot and irradiated with blue light for 24 h. Afterwards, each sample was analysed according to the GC/MS procedure.

Photocatalytic C-C Bond Coupling
For each reaction, polymer stock solution (300 µL, 10 mg polymer, 75.3 µg photocatalyst) was given into a 4 mL screw-cap vial, equipped with a stir bar. Followed by addition of water (Milli-Q, 1.7 mL), triethylamine (10 Eq., 15 µL), solvent additive (15µL) and the halogen substrate to give a 5 mM solution(0.6 mol% photocatalyst). Under constant stirring at 450 rpm, and cooling to 15 °C, the vials were placed into a photoreactor slot and irradiated with blue light for 24 h. Afterwards, each sample was analysed according to the GC/MS procedure.

Tetrahydrothiophene 1-oxide
The synthesis of tetrahydrothiophene 1-oxide was performed according to the general procedure for photocatalytic sulfide oxidations, explained in SI section 9.1. The purification of the compound was performed by flash column chromatography (Hexane: EtOAc, 9:1) with potassium permanganate staining.

N-benzyl-1-phenylmethanimine
The synthesis of N-benzyl-1-phenylmethanimine was performed according to the general procedure for photocatalytic imine formation, explained in SI section 9.2. The purification of the compound was performed by flash column chromatography (Hexane: EtOAc, 6:4).